1. Field of the Invention
The invention relates in general to a method and a device for preparing microspheres as well as a collection unit thereof, and more particularly to a method and a device for preparing microspheres in a continuous manner as well as a collection unit thereof.
2. Description of the Related Art
Microcapsules and Microspheres formed from various natural or synthetic polymers and resins have become popular delivery vehicles for various active materials such as drugs, diagnostic reagents, and the like. Biodegradable microcapsules and microspheres are for use in so called depot formulations, where delivery of the active material over an extended period of time is desired.
Processes for preparing microspheres usually involve the formation of at least one dispersed phase in a continuous phase. The dispersed phase usually includes the active material and polymer and, upon solidification in the continuous phase, becomes a microsphere. Microcapsules are similarly formed using multiple phases. In a conventional practice, a water-oil-water (w/o/w) emulsion is formed, and the polymer caused to precipitate out of one phase onto the surface of a dispersed phase to form a capsule wall thereon upon solidification of the polymer.
In 1980, a biodegradable polymer, poly(lactic/glycolic acid) (PLGA), was first developed and utilized to encapsulate leuprolide acetate, by Takeda pharmaceutical company, Japan. In the process of preparing product, sustained-release microcapsules, in which a water-oil-water (w/o/w) double emulsion is used to encapsulate drugs, are employed. In the process of solidifying microcapsules, the drugs and the first emulsion of PLGA are introduced into polyvinyl alcohol (PVA) where the PLGA is emulsified at the second time, and the capsules are solidified by drying in liquid process.
Because there will be drugs and PVA remained on the surface of the microcapsules, clean water is usually mixed in to clean the microcapsules, and the microcapsules are collected by centrifugalization. However, the capsules with PLGA polymer do not have enough hardness, which causes the problems of deformation and aggregation of capsules after centrifugalization.
Moreover, centrifugally collecting capsules is required to be operated by personnel. Operation process thereof includes: distributing the solidified microcapsules and solution into several centrifugal tubes; carefully removing the supernatant from each tube after centrifugalization; introducing a small amount of certain solution so as to suspend the microcapsules again; collecting the microcapsules; and making the microcapsules into powder by drying. The conventional process in fact belongs to a batch process, which requires an operator to manipulate the centrifugal machine to complete the steps of collecting microcapsules, thereby increasing manufacturing cost, failing to establish a continuous preparing process due to its collecting behavior, and causing a limit to production scale thereof. Furthermore, the produced microcapsules have the problem of deformation or aggregation, which also negatively affects the release model of drugs.